This project aimed to characterize the receptors for Phe-Met-Arg-Phe-NH2, (FMRFamide) and Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, in molluscan and mammalian CNS, respectively. The FMRFamide receptors in squid optic lobe were determined to be coupled to stimulation of adenylate cyclase through a membrane G-protein, and had ligand binding preferences similar to those in Helix aspersa. Radioactive photoaffinity ligands were used to label the optic lobe FMRFamide receptor, which appears to be a 52,000 MW protein that can be solubilized by Triton X-100. Adenylate cyclase activity of rat spinal cord membranes was unaffected by NPFF, whereas kappa opioid dynorphins weakly inhibited AC activity. In 1 of 2 experiments on isolated terminals of rat neural lobe, dynorphin A 1-8 inhibited vasopressin and oxytocin secretion stimulated by high potassium, and this inhibition was reversed by NPFF or naloxone. A putative NPFF antagonist (daY8Ra) attenuated the NPFF-induced opiate abstinence syndrome in naive rats. High dosage, however, caused NPFF-like abstinence symptoms. Interestingly, daY8Ra also blocked the naloxone-induced withdrawal symptoms in morphine-dependent rats, suggesting that NPFF is involved in the expression of withdrawal syndrome in both normal and dependent rats.